Pain sensation is typically the result of peripherally generated neural stimuli, which are transmitted therefrom and modulated in the CNS before arriving in the cortex and in the consciousness. Tests for modulation mechanisms known in the art include the diffuse noxious inhibitory control (DNIC). Diffuse noxious inhibitory control (DNIC) represents the endogenous analgesia system, where modulatory effect is exerted on incoming spinal nociceptive neural stimuli. This phenomenon is based on a spinal-bulbar-spinal loop, under cerebral control, which, at least partially, is opioid-mediated. DNIC is typically tested in the lab using the ‘pain inhibits pain’ paradigm, by two remote noxious stimuli, the ‘conditioning’ pain on the one hand, and on the other hand an inhibiting one, the ‘test’ pain.
Pain summation is complex as two adjacent nociceptive stimuli cause an additive effect, whereas two remote nociceptive stimuli cause an inhibitory effect. Neuroanatomical distribution is associated with this process. Temporally-wise, a certain frequency makes a difference between summation and adaptation for a specific stimulus
Therapy for neuropathic pain, despite newly presented drugs, is still frustrating, with less than half of the patients not achieving satisfactory relief; possibly due to the lack of mechanism-oriented choice of therapy. Currently, it is mainly the consideration of side effects which inspires the physician in choosing the anti-neuropathic pain medication, rather than, ideally, its mechanism of action. Several lines of pharmacological therapy are recommended for neuropathic pain; antidepressants, antiepileptics and opioids.
Antidepressants include tricyclics and SNRIs (Serotonin and noradrenaline reuptake Inhibitor), since SSRIs (selective serotonin reuptake inhibitors) have proven less effective in treating neuropathic pain. Tricyclics have been the mainstay of therapy for many years, giving a fairly good number need to treat (NNT) of 2-3, but with considerable adverse effects especially in older patients (Watson et al., 1998). SNRIs such as the medicines commercialized under trademarks of Venlafaxine and Duloxetine which have proven as effective for neuropathic pain, mainly for diabetic neuropathy (Goldstein et al., 2005), with a slightly less favourable NNT (4-6), but more favourable side effect profile (Wernicke et al., 2007). The mechanism of action of both tricyclics and SNRIs is to increase synaptic levels of both serotonin (5-hdroxytryptamine or 5-HT) and noradrenaline (NA), via a dual inhibition of their reuptake in the CNS. An increased level of these neurotransmitters exerts descending modulation via the bulbo-spinal tracts, augmenting the inhibitory effect on pain perception. Of the antiepileptics, the medications that seem to be most relevant for neuropathic pain are gabapentin (GBP) and pregabalin (PGB) (Chandra et al., 2006), whereas the medicines commercialized under trademarks of oxcarbamazepine and lamotrigine showed lesser effects (Viniket al., 2007). PGB and GBP inhibit the presynaptic α-2-δ subunit of the Ca channel, and are therefore expected to diminish effects that depend on calcium influx, including central sensitization. The role of opioids in neuropathic pain is still controversial; while convincing evidence has been accumulated in recent years for efficacy in neuropathic pain, the safety profile is still unclear, leading the recent EFNS guideline to recommend opioids as second line medications for neuropathic pain (Attal et al., 2006).
Accordingly, implementation of the DNIC phenomenon for assessing the pain modulation profile of a patient as well as for clinically beneficially modulating the pain sensation and to provide relief for pain-inflicted patients, in addition or as an alternative to the pharmaceutical treatment, is called for.